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Related Collections Hemostasis, Thrombosis, and Vascular Biology Plenary Papers Gene Therapy Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2002, Vol. 99, No. 8, pp. 2670-2676 PLENARY PAPER Sustained phenotypic correction of hemophilia B dogs with a factor IX null mutation by liver-directed gene therapy Jane D. Mount, Roland W. Herzog, D. Michael Tillson, Susan A. Goodman, Nancy Robinson, Mark L. McCleland, Dwight Bellinger, Timothy C. Nichols, Valder R. Arruda, Clinton D. Lothrop Jr, and Katherine A. High From the Scott-Ritchey Research Center and Department of Clinical Sciences. College of Veterinary Sciences, Auburn University, AL; Departments of Pediatrics and Pathology, University of Pennsylvania Medical Center and The Children's Hospital of Philadelphia; and Department of Laboratory Medicine and Pathology, University of North Carolina, Chapel Hill. Hemophilia B is an X-linked coagulopathy caused by absence of functional coagulation factor IX (FIX). Using adeno-associated virus (AAV)-mediated, liver-directed gene therapy, we achieved long-term (> 17 months) substantial correction of canine hemophilia B in 3 of 4 animals, including 2 dogs with an FIX null mutation. This was accomplished with a comparatively low dose of 1 × 1012 vector genomes/kg. Canine FIX (cFIX) levels rose to 5% to 12% of normal, high enough to result in nearly complete phenotypic correction of the disease. Activated clotting times and whole blood clotting times were normalized, activated partial thromboplastin times were substantially reduced, and anti-cFIX was not detected. The fourth animal, also a null mutation dog, showed transient expression (4 weeks), but subsequently developed neutralizing anti-cFIX (inhibitor). Previous work in the canine null mutation model has invariably resulted in inhibitor formation following treatment by either gene or protein replacement therapies. This study demonstrates that hepatic AAV gene transfer can result in sustained therapeutic expression in a large animal model characterized by increased risk of a neutralizing anti-FIX response. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: The liver sieve and gene therapy Robin Fraser, David G. Le Couteur, Alessandra Warren, Victoria C. Cogger, Patrick Bertolino, Mark Smith, Katherine A. High, Roland Herzog, and Valder Arruda Blood 2003 101: 3338. [Full Text] [PDF] This article has been cited by other articles: F. Mingozzi, J. J. Meulenberg, D. J. Hui, E. Basner-Tschakarjan, N. C. Hasbrouck, S. A. Edmonson, N. A. Hutnick, M. R. Betts, J. J. Kastelein, E. S. Stroes, et al. 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